한빛사논문
- 조회584
JinsuKim1,7, Katherine M. Sheu2,3,7, Quen J. Cheng2,4, Alexander Hoffmann2,3,8, German Enciso5,6,8,9
1Department of Mathematics, Pohang University of Science and Technology, Pohang, South Korea
2Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA
3Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA
4Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, Los Angeles, CA, USA
5Department of Mathematics, University of California, Irvine, Irvine, CA, USA
6Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA
7These authors contributed equally
8Senior author
9Lead contact
Corresponding authors : Alexander Hoffmann, German Enciso
Abstract
The genomic positions of nucleosomes are a defining feature of the cell’s epigenomic state, but signal-dependent transcription factors (SDTFs), upon activation, bind to specific genomic locations and modify nucleosome positioning. Here we leverage SDTFs as perturbation probes to learn about nucleosome dynamics in living cells. We develop Markov models of nucleosome dynamics and fit them to time course sequencing data of DNA accessibility. We find that (1) the dynamics of DNA unwrapping are significantly slower in cells than reported from cell-free experiments, (2) only models with cooperativity in wrapping and unwrapping fit the available data, (3) SDTF activity produces the highest eviction probability when its binding site is adjacent to but not on the nucleosome dyad, and (4) oscillatory SDTF activity results in high location variability. Our work uncovers the regulatory rules governing SDTF-induced nucleosome dynamics in live cells, which can predict chromatin accessibility alterations during inflammation at single-nucleosome resolution.
논문정보
- Research article
- 2022년 07월 (BRIC 등록일 2022-12-13)
- 국내+국외 연구진
- 생명과학 > 세포생물학
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